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Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways.
Environ Toxicol Pharmacol. 2018 Mar; 58:212-219.ET

Abstract

Cadmium (Cd) intoxication in human occurs through inhalation of cigarette smoke and ingestion of contaminated water and food. We investigated the role of nebivolol (NEB) in Cd induced hepatotoxicity. In our study; NEB was given as (10 mg/kg/d) orally to rats for 6 weeks, in the presence or absence of hepatotoxicity induced by oral administration of Cd (7 mg/kg/d) for 6 weeks. Levels of serum liver enzyme biomarkers; alanine transaminase (ALT), aspartate transaminase (AST) and serum total antioxidant capacity (TAC) were measured. In addition; mean arterial pressure and total cholesterol levels were measured. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. Hepatic histopathological features, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoexpressions were evaluated. Tumor necrosis factor alpha (TNF-α) and B-cell lymphoma-2 (Bcl-2) mRNA gene expressions were detected using real time-PCR (rt-PCR). Our results showed marked increase in all measured parameters except SOD, TAC, eNOS immunoexpression and Bcl2 mRNA gene expression which decreased in Cd induced hepatotoxicity group. NEB showed marvelous protective effect against Cd induced changes. NEB decreased liver enzymes (ALT and AST), mean arterial pressure, total cholesterol levels, MDA, iNOS immunoexpression and TNF-α gene expression but significantly increased SOD, TAC, eNOS immunoexpression and Bcl-2 gene expression. Moreover; NEB markedly improved the histopathological changes induced by Cd. These findings prove the antioxidant, anti-apoptotic and anti-inflammatory properties of NEB and its protective role in Cd induced hepatotoxicity.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt. Electronic address: marwamonier@yahoo.com.Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt. Electronic address: sama_feb.2009@yahoo.com.Department of Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt. Electronic address: nagwa_zenhom@yahoo.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29408764

Citation

Refaie, Marwa M M., et al. "Protective Role of Nebivolol in Cadmium-induced Hepatotoxicity Via Downregulation of Oxidative Stress, Apoptosis and Inflammatory Pathways." Environmental Toxicology and Pharmacology, vol. 58, 2018, pp. 212-219.
Refaie MMM, El-Hussieny M, Zenhom NM. Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways. Environ Toxicol Pharmacol. 2018;58:212-219.
Refaie, M. M. M., El-Hussieny, M., & Zenhom, N. M. (2018). Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways. Environmental Toxicology and Pharmacology, 58, 212-219. https://doi.org/10.1016/j.etap.2018.01.011
Refaie MMM, El-Hussieny M, Zenhom NM. Protective Role of Nebivolol in Cadmium-induced Hepatotoxicity Via Downregulation of Oxidative Stress, Apoptosis and Inflammatory Pathways. Environ Toxicol Pharmacol. 2018;58:212-219. PubMed PMID: 29408764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways. AU - Refaie,Marwa M M, AU - El-Hussieny,Maram, AU - Zenhom,Nagwa M, Y1 - 2018/02/01/ PY - 2017/09/12/received PY - 2018/01/23/revised PY - 2018/01/30/accepted PY - 2018/2/7/pubmed PY - 2018/8/28/medline PY - 2018/2/7/entrez KW - Apoptosis KW - Cadmium KW - Endothelial nitric oxide synthase KW - Inducible nitric oxide synthase KW - Nebivolol KW - Oxidative stress SP - 212 EP - 219 JF - Environmental toxicology and pharmacology JO - Environ Toxicol Pharmacol VL - 58 N2 - Cadmium (Cd) intoxication in human occurs through inhalation of cigarette smoke and ingestion of contaminated water and food. We investigated the role of nebivolol (NEB) in Cd induced hepatotoxicity. In our study; NEB was given as (10 mg/kg/d) orally to rats for 6 weeks, in the presence or absence of hepatotoxicity induced by oral administration of Cd (7 mg/kg/d) for 6 weeks. Levels of serum liver enzyme biomarkers; alanine transaminase (ALT), aspartate transaminase (AST) and serum total antioxidant capacity (TAC) were measured. In addition; mean arterial pressure and total cholesterol levels were measured. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. Hepatic histopathological features, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoexpressions were evaluated. Tumor necrosis factor alpha (TNF-α) and B-cell lymphoma-2 (Bcl-2) mRNA gene expressions were detected using real time-PCR (rt-PCR). Our results showed marked increase in all measured parameters except SOD, TAC, eNOS immunoexpression and Bcl2 mRNA gene expression which decreased in Cd induced hepatotoxicity group. NEB showed marvelous protective effect against Cd induced changes. NEB decreased liver enzymes (ALT and AST), mean arterial pressure, total cholesterol levels, MDA, iNOS immunoexpression and TNF-α gene expression but significantly increased SOD, TAC, eNOS immunoexpression and Bcl-2 gene expression. Moreover; NEB markedly improved the histopathological changes induced by Cd. These findings prove the antioxidant, anti-apoptotic and anti-inflammatory properties of NEB and its protective role in Cd induced hepatotoxicity. SN - 1872-7077 UR - https://www.unboundmedicine.com/medline/citation/29408764/Protective_role_of_nebivolol_in_cadmium_induced_hepatotoxicity_via_downregulation_of_oxidative_stress_apoptosis_and_inflammatory_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1382-6689(18)30018-8 DB - PRIME DP - Unbound Medicine ER -